rtPA in in the Prevention of CVAD-Associated Thrombosis and Infection in Pediatric Patients With Short Bowel Syndrome

Central venous access devices (CVAD) are used routinely in chronically ill pediatric patients
for administration of medications, parenteral nutrition and laboratory testing. Several
complications resulting from the use of long-term CVADs, namely venous sepsis and thrombosis,
can significantly increase associated morbidity and mortality. CVAD-associated thrombosis
occurs in up to 50% of children with long-term CVAD use and this is especially common in
patients requiring life-sustaining long-term total parenteral nutrition (1). Catheter
thrombosis may arise from fibrin sheath formation around the catheter tip, intraluminal blood
clot within the catheter, or venous thrombosis obstructing the vein and occluding the
catheter tip. Within 24 hours and typically within 2 weeks of placement of a CVAD, a fibrin
sheath forms around its tip (2-5). Development of intraluminal thrombosis or venous
thrombosis is less predictable.

There is a growing body of evidence linking the development of CVAD-associated thrombosis and
line-related infection. It is known that proteins within the thrombus including fibronectin
and fibrinogen attract bacteria, specifically staphylococcal species. The bacteria bind to
ligands associated with the thrombus thus allowing for bacterial proliferation (6-8). The
clinical relevance of line thrombus in development of line infection is underscored in a
study of pediatric patients with Hickman catheters, of whom 18% with catheter thrombosis
developed a line-associated bloodstream infection, while none developed a catheter infection
that did not also have a catheter clot (7). Thus, we hypothesize that prevention of
catheter-related clot formation with use of a local thrombolytic agent will also prevent
infection in the catheter.

The primary research question we pose is, in patients with short bowel syndrome requiring
central venous access device (CVAD) for long-term total parenteral nutrition, is once weekly
recombinant tissue plasminogen activator (rtPA) lock therapy more effective than routine care
using heparin flushes in reducing the incidence of line-associated thrombosis and infection.

Inclusion Criteria:

1. subjects with short bowel syndrome

2. requirement for central venous access device (CVAD) for long-term TPN administration

3. age >/= 6 months to < 16 years

4. ability to initiate rtPA during hospitalization for newly inserted CVAD

5. ability to be enrolled within 48 hours of CVAD placement.

Exclusion Criteria:

1. platelet count <50,000

2. active bleeding

3. age =/> 16 years at time of consent.